caa a22 4500 465764797 CHVBK 20180323111910.0 cr unu---uuuuu 170327e19900101xx s 000 0 eng 10.1007/BF00155588 doi (NATIONALLICENCE)springer-10.1007/BF00155588 Israel L. 10585ique Universitaire de Cancérologie, Université Paris Nord, Hôpital Avicenne, 125, route de Stalingrad, 93000, Bobigny, France aut Accelerated genetic destabilization and dormancy: two distinct causes of resistance in metastatic cells; 10585ical magnitude, therapeutic approaches [Elektronische Daten] [L. Israel] Several years of 10585ical chemotherapy have shown that, despite modern refinements, cytotoxic agents are not able to eradicate metastases of most adult solid tumors but only to prolong survival by achieving a cell kill that is not 100 per cent. Among the possible causes of this phenomenon, two are discussed in detail. The first one is cell autonomy. It is shown that the numbers of generations reached by a metastatic clone until 10585ical detection is largely in excess of 100, which allows for a considerable number of mutations, and that in addition genetic destabilization leading to autonomy proceeds much more rapidly than anticipated by a random mutation process. Adaptative changes by genetic amplification in response to toxic injury add to this acceleration effect, accounting for the fact that most metastatic cells are totally resistant very early in the natural history of a human tumor. On the other hand, it is shown that dormant metastatic cells do exist, due either to lack of autocrine growth factors or to inhibiting agents secreted by other metastases. These cells can survive chemotherapy and then re-enter a proliferative state due to some mechanisms that are analyzed, accounting for semi-late and late failures. These obstacles call for other strategies of metastases management, such as arresting or differentiating agents, some of which have been successfully tested by the author's group, such as antiprostaglandins, antithrombin, somatostatin, hyaluronidase, and retinoic acid. It remains to study their optimal combinations, and the appropriate timing, in order to achieve, if not eradication, growth suppression for very long periods without toxicity. Taylor & Francis Ltd, 1990 Clinical & Experimental Metastasis Kluwer Academic Publishers 8/1(1990-01-01), 1-11 0262-0898 8:1<1 1990 8 10585 https://doi.org/10.1007/BF00155588 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00155588 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Israel L. 10585ique Universitaire de Cancérologie, Université Paris Nord, Hôpital Avicenne, 125, route de Stalingrad, 93000, Bobigny, France aut NATIONALLICENCE 773 0- Clinical & Experimental Metastasis Kluwer Academic Publishers 8/1(1990-01-01), 1-11 0262-0898 8:1<1 1990 8 10585 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer